The symbiotic Wolbachia in Anopheles and its role in reducing the transmission of Plasmodium: updates and prospects

Reducing malaria transmission and the prospects for vector control include multi-pronged strategies, such as interrupting the parasite cycle in both vectors and mosquitoes. Effective vector control remains essential to prevent malaria transmission. This is all the more important as problems such as resistance to insecticides and the lack of a highly effective malaria vaccine remain. New generation vector control measures and optimised products are essential to address the public health needs for malaria eradication. Strategies to reduce malaria transmission include the use of insecticide-treated nets (ITNs), indoor residual spraying (IRS) and other measures. Recent studies have shown that Wolbachia pipientis, a bacterium that acts as an intracellular endosymbiotic in host cells, is becoming increasingly popular as a new method of control for Anopheles mosquitoes, both for cytoplasmic incompatibility and for pathogen blocking. Anopheles gambiae, the infection rate ranged from 8 to 24% in the wild population of the same study in the case of An. coulzzi (WAnga) in Ghana, with a prevalence of 4%. Various studies have successfully identified Wolbachia in several species of Anopheles. A highly infected Anopheles species A population in the Democratic Republic of the Congo (DRC) showed a 91% infection rate (strain wAnsA). Broader surveys list additional species hosting natural Wolbachia, including An. funestus, An. moucheti, An. melas, An. nili, An. coustani, An. dirus, An. baimaii, An. hyrcanus, and An. sinensis, among others, totalling around 31 Anopheles species. In Anopheles stephensi, researchers achieved stable maternal transmission of the wPip strain with a 100% infection frequency in the transinfected line across generations. The infection caused nearly complete cytoplasmic incompatibility (CI) and moderate fitness costs. Previous experimental infections using the wAlbB strain in An. stephensi similarly established CI and partial protection against Plasmodium infection. Wolbachia has been detected naturally at low prevalence (~ 1.4%) in field-collected An. culicifacies samples in India. However, these infections are often rare and may not lead to a high blocking effect of the pathogens. Despite the notable progress in demonstrating the CI and moderate inhibitory effect of the pathogen in several Anopheles trans-infected lines, the remaining setbacks include persistent, mother-transmitted infection with a high population replacement or suppression potential that will be relevant for widespread use. This comprehensive evaluation identified the need for further research on host-symbiotic interactions, improved genetic engineering tools and comprehensive long-term field evaluations to fully realise the potential of Wolbachia as a vector control tool for malaria.